Department of Chemistry, University of California, Irvine, Irvine, California, United States of America.
Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica.
PLoS Negl Trop Dis. 2018 Oct 4;12(10):e0006736. doi: 10.1371/journal.pntd.0006736. eCollection 2018 Oct.
Envenomings by snakebites constitute a serious and challenging global health issue. The mainstay in the therapy of snakebite envenomings is the parenteral administration of animal-derived antivenoms. Significantly, antivenoms are only partially effective in the control of local tissue damage. A novel approach to mitigate the progression of local tissue damage that could complement the antivenom therapy of envenomings is proposed. We describe an abiotic hydrogel nanoparticle engineered to bind to and modulate the activity of a diverse array of PLA2 and 3FTX isoforms found in Elapidae snake venoms. These two families of protein toxins share features that are associated with their common (membrane) targets, allowing for nanoparticle sequestration by a mechanism that differs from immunological (epitope) selection. The nanoparticles are non-toxic in mice and inhibit dose-dependently the dermonecrotic activity of Naja nigricollis venom.
蛇伤导致的中毒是一个严重且具有挑战性的全球健康问题。蛇伤中毒治疗的主要方法是通过注射动物源性抗蛇毒血清。值得注意的是,抗蛇毒血清在控制局部组织损伤方面的效果仅部分有效。为了减轻局部组织损伤的进展,我们提出了一种新的方法,以补充蛇伤的抗蛇毒血清治疗。我们描述了一种非生物水凝胶纳米颗粒,该纳米颗粒经过设计,可与存在于眼镜蛇科蛇毒中的多种 PLA2 和 3FTX 同工型结合,并调节其活性。这两种蛋白毒素家族具有与其共同(膜)靶标相关的特征,允许通过不同于免疫(表位)选择的机制进行纳米颗粒的隔离。这些纳米颗粒在小鼠中无毒性,并能剂量依赖性地抑制眼镜蛇科蛇毒的皮肤坏死活性。